Kappa-opioid receptor blockade in the inferior colliculus of prey threatened by pit vipers decreases anxiety and panic-like behaviour.

The dorsal midbrain comprises dorsal columns of the periaqueductal grey matter and corpora quadrigemina. These structures are rich in beta-endorphinergic and leu-enkephalinergic neurons and receive GABAergic inputs from substantia nigra pars reticulata. Although the inferior colliculus (IC) is mainly involved in the acoustic pathways, the electrical and chemical stimulation of central and pericentral nuclei of the IC elicits a vigorous defensive behaviour. The defensive immobility and escape elicited by IC activation is commonly related to panic-like emotional states. To investigate the role of κ-opioid receptor of the IC in the antiaversive effects of endogenous opioid receptor blockade in a dangerous situation, male Wistar rats were pretreated in the IC with the κ-opioid receptor-selective antagonist nor-binaltorphimine at different concentrations and submitted to the non-enriched polygonal arena for a snake panic test in the presence of a rattlesnake and, after 24 h, prey were resubmitted to the experimental context. The snakes elicited in prey a set of antipredatory behaviours, such as the anxiety-like responses of defensive attention and risk assessment, and the panic-like reactions of defensive immobility and either escape or active avoidance during the elaboration of unconditioned and conditioned fear-related responses. Pretreatment of the IC with microinjections of nor-binaltorphimine at higher concentrations significantly decreased the frequency and duration of both anxiety- and panic-attack-like behaviours. These findings suggest that κ-opioid receptor blockade in the IC causes anxiolytic- and panicolytic-like responses in threatening conditions, and that kappa-opioid receptor-selective antagonists can be a putative coadjutant treatment for panic syndrome treatment.

Application value of opioid-free anesthesia in renal cyst decompression by laparoscopy.

Objective: The objective of the study was to analyze the application value of opioid-free anesthesia (OFA) in renal cyst decompression by laparoscopy. Method: A total of 124 patients undergoing renal cyst decompression by laparoscopy in our hospital were selected and divided into opioid anesthesia (OA) and OFA groups (n = 62). Fentanyl and remifentanil were used for anesthesia induction in the OA group, while lidocaine and dexmedetomidine were employed for anesthesia induction in the OFA group. The homeostasis indicators (cortisol [Cor], adrenocorticotropic hormone [ACTH], C-reactive protein [CRP], and interleukin-6 [IL-6]) were also compared 10 min before anesthesia (Ta), at the end of operation (Tb), and 24 h after operation (Tc). Results: At T1-T3, heart rate, mean arterial pressure, mean airway pressure, and partial pressure of end-tidal carbon dioxide were all lower in OFA group than those in OA group (p < 0.05). At Tb-Tc, the levels of Cor, ACTH, CRP, and IL-6 were all higher in both groups than those at Ta (p < 0.05), while they were lower in OFA group than those in OA group (p < 0.05). Conclusion: OFA is more beneficial to the respiratory and circulatory system and homeostasis of patients, and has higher anesthetic safety.

[Efficacy of transdermal lidocaine 5% patches in postoperative analgesia following knee arthroscopy]. / Efectividad del parche transdérmico de lidocaína 5% en la analgesia postoperatoria después de la artroscopía de rodilla.

INTRODUCTION: knee arthroscopy is a common orthopedic procedure associated with postoperative pain, so optimizing pain management is essential for patient recovery and satisfaction. Lidocaine, a local anesthetic with well-established safety profiles, offers a potential alternative to traditional analgesic methods. Research regarding lidocaine patches has been conducted in several types of surgeries (laparoscopy, gynecological surgery, prostatectomy, etc.) showing promising results for some. This study investigates the effectiveness of transdermal lidocaine 5% patches as a novel approach to postoperative analgesia after knee arthroscopy. MATERIAL AND METHODS: a randomized, single-blind, placebo-controlled trial was conducted with participants undergoing knee arthroscopy. Patients were divided into two groups: one receiving transdermal lidocaine 5% patches and the other a placebo, both along traditional postoperative pain management, and using opioid only in cases with moderate-severe pain. Pain scores, opioid consumption, and patient-reported outcomes were assessed at various postoperative intervals. RESULTS: there was a significant reduction in pain scores and opioid consumption in the lidocaine patch group compared to the placebo group. CONCLUSIONS: transdermal lidocaine 5% patches emerge as a promising adjunct to postoperative pain management in knee arthroscopy patients. Their ease of application, minimal side effects, and opioid-sparing effects contribute to a multifaceted analgesic approach. This study underscores the potential of transdermal lidocaine patches in enhancing the overall postoperative experience for knee arthroscopy patients, advocating for their consideration in clinical practice.

INTRODUCCIÓN: la artroscopía de rodilla es un procedimiento ortopédico común asociado con dolor postoperatorio, por lo que optimizar el manejo del dolor es esencial para la recuperación y la satisfacción del paciente. La lidocaína, un anestésico local con perfiles de seguridad bien establecidos, ofrece una alternativa potencial a los métodos analgésicos tradicionales. Se ha llevado a cabo investigación sobre los parches de lidocaína en diversos tipos de cirugías (laparoscopía, cirugía ginecológica, prostatectomía, etcétera), mostrando resultados prometedores en algunos casos. MATERIAL Y MÉTODOS: se realizó un ensayo clínico aleatorizado, ciego simple y controlado con placebo que incluyó participantes sometidos a artroscopía de rodilla. Los pacientes fueron divididos en dos grupos: uno recibió parches transdérmicos de lidocaína al 5% y otro un placebo, ambos junto con el manejo tradicional del dolor postoperatorio y utilizando opioides sólo en casos de dolor moderado a severo. Se evaluaron las puntuaciones de dolor, el consumo de opioides y los resultados informados por los pacientes en varios intervalos postoperatorios. RESULTADOS: se registró una reducción significativa en las puntuaciones de dolor y el consumo de opioides en el grupo de parches de lidocaína en comparación con el grupo de placebo. CONCLUSIONES: los parches transdérmicos de lidocaína al 5% emergen como un complemento prometedor para el manejo del dolor postoperatorio en pacientes sometidos a artroscopía de rodilla. Su facilidad de aplicación, mínimos efectos secundarios y efectos ahorradores de opioides contribuyen a un enfoque analgésico multifacético. Este estudio destaca el potencial de los parches de lidocaína transdérmica para mejorar la experiencia postoperatoria general de los pacientes con artroscopía de rodilla, abogando por su consideración en la práctica clínica.

The Use of Natural Language Processing Methods in Reddit to Investigate Opioid Use: Scoping Review.

BACKGROUND: The growing availability of big data spontaneously generated by social media platforms allows us to leverage natural language processing (NLP) methods as valuable tools to understand the opioid crisis. OBJECTIVE: We aimed to understand how NLP has been applied to Reddit (Reddit Inc) data to study opioid use. METHODS: We systematically searched for peer-reviewed studies and conference abstracts in PubMed, Scopus, PsycINFO, ACL Anthology, IEEE Xplore, and Association for Computing Machinery data repositories up to July 19, 2022. Inclusion criteria were studies investigating opioid use, using NLP techniques to analyze the textual corpora, and using Reddit as the social media data source. We were specifically interested in mapping studies' overarching goals and findings, methodologies and software used, and main limitations. RESULTS: In total, 30 studies were included, which were classified into 4 nonmutually exclusive overarching goal categories: methodological (n=6, 20% studies), infodemiology (n=22, 73% studies), infoveillance (n=7, 23% studies), and pharmacovigilance (n=3, 10% studies). NLP methods were used to identify content relevant to opioid use among vast quantities of textual data, to establish potential relationships between opioid use patterns or profiles and contextual factors or comorbidities, and to anticipate individuals' transitions between different opioid-related subreddits, likely revealing progression through opioid use stages. Most studies used an embedding technique (12/30, 40%), prediction or classification approach (12/30, 40%), topic modeling (9/30, 30%), and sentiment analysis (6/30, 20%). The most frequently used programming languages were Python (20/30, 67%) and R (2/30, 7%). Among the studies that reported limitations (20/30, 67%), the most cited was the uncertainty regarding whether redditors participating in these forums were representative of people who use opioids (8/20, 40%). The papers were very recent (28/30, 93%), from 2019 to 2022, with authors from a range of disciplines. CONCLUSIONS: This scoping review identified a wide variety of NLP techniques and applications used to support surveillance and social media interventions addressing the opioid crisis. Despite the clear potential of these methods to enable the identification of opioid-relevant content in Reddit and its analysis, there are limits to the degree of interpretive meaning that they can provide. Moreover, we identified the need for standardized ethical guidelines to govern the use of Reddit data to safeguard the anonymity and privacy of people using these forums.

Comparison of the recovery profile of sufentanil and remifentanil in total intravenous anesthesia: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Remifentanil is a short-acting opioid and can be administered during surgery without the risk of delayed postoperative recovery but concerns about hyperalgesia and the shortages of remifentanil lead anesthetists to consider long-acting opioids for Total Intravenous Anesthesia (TIVA). Sufentanil is a more potent opioid with a longer context-sensitive half-life but can promote good postoperative analgesia due to its residual effect. This meta-analysis aimed to compare the recovery profile of remifentanil and sufentanil for TIVA. METHODS: The search strategy was performed in PubMed, CENTRAL, and Web of Science for RCTs comparing sufentanil and remifentanil as part of TIVA in adults undergoing noncardiac surgery. Risk of bias and the quality of evidence were performed using RoB2 and GRADEpro, respectively. The primary outcome was time to tracheal extubation. Secondary analyses included postoperative analgesia, respiratory depression, and Postoperative Nausea and Vomiting (PONV). RESULTS: Sufentanil increases the time to extubate, MD = 4.29 min; 95% CI: 2.33 to 6.26; p = 0.001. It also reduces the need for postoperative rescue analgesia, logOR = -1.07; 95% CI: -1.62 to -0.52; p = 0.005. There were no significant differences between both opioids for PONV, logOR = 0.50; 95% CI: -0.10 to 1.10; p = 0.10 and respiratory depression, logOR = 1.21; 95% CI: -0.42 to 2.84; p = 0.15. CONCLUSION: Sufentanil delays the time to tracheal extubation compared with remifentanil but is associated with a reduced need for postoperative rescue analgesia. No significant differences were observed between the two opioids in terms of postoperative respiratory depression or PONV.

The use of naltrexone in the treatment of chronic pain: a systematic review.

This study aims to assess the efficacy of low-dose naltrexone (LDN) in treating chronic pain. We conducted a systematic review using the PICO strategy: (P) Patients with chronic pain, (I) Use of oral naltrexone, (C) Placebo or active drug and (O) Pain relief and quality of life. We included articles from PubMed, Scopus, Cochrane CENTRAL and EMBASE databases. Seven randomized clinical trials involving 406 patients were analyzed. The doses ranging from 2 to 4.5 mg once daily across all studies. Various chronic pain conditions were evaluated. The results suggest that low-dose naltrexone is not effective in managing chronic pain and improving the quality of life in patients with diverse chronic pain conditions. However, further research with larger sample sizes and standardized methodologies is necessary.

This study looks at how well low-dose naltrexone (LDN) works for treating long-lasting pain. We reviewed research where patients with chronic pain were given either LDN or a placebo (a fake treatment). We found eight studies that included a total of 421 patients. The LDN doses used ranged from very small amounts 2­4.5 mg, taken once a day. These studies looked at different types of chronic pain. Our results suggest that LDN cannot help to reduce pain and improve the quality of life for people with chronic pain. However, more research with larger groups of people and consistent methods is needed to confirm these findings.

Impact of disabilities in activities of daily living on opioid use for chronic pain in older adults: an exploratory secondary analysis from ELSI-Brazil.

OBJECTIVES: Problematic use of opioids by older adults is associated with adverse effects and has become a public health crisis worldwide. Ageing-related disabilities in activities of daily living (ADL) could promote unnecessary use of opioids in this population. This study evaluates the association between ADL disability and opioid consumption in Brazilian older adults. STUDY DESIGN: Study design- cross-sectional secondary data analysis of the second wave of the Brazil Longitudinal Study of Ageing (ELSI-Brazil). METHODS: Data from the second wave of the Brazil Longitudinal Study of Ageing (ELSI-Brazil) were used. Older adults with chronic pain were included. ADL disability was measured using the Katz Index. The primary outcome was opioid consumption for chronic pain. The primary association was explored using logistic regression models adjusting for predetermined confounders. Sensitivity analyses evaluating model performance were done by calibrating and validating the model using randomly split equal sets. RESULTS: In those who reported presence of chronic pain (n = 2865), the prevalence of opioid use was 29% (95% CI:23.1%-35.6%). In adjusted models, participants with moderate and severe ADL disability had 1.6 (95% CI:1.13-2.32; P = 0.009) and 3.8 (95% CI: 1.80-7.90; P < 0.001) times higher odds of opioid consumption compared to no disability, respectively. Being female, alcohol consumption, higher pain intensity, history of dementia, fractures, and presence of ≥2 comorbidities were significantly associated with increased opioid use (P < 0.05). CONCLUSION: Nearly one-third of the Brazilian elderly population experiencing chronic pain reported using opioids. The functional decline during the process of ageing appears to be a risk factor for pain intolerance and opioid use. Multidisciplinary approaches to detect early ADL disabilities and improve mobility and access to assistive technologies need to be established to prevent opioid overuse and addiction in elderly populations.

Modified thoracoabdominal nerve block via perichondral approach: an alternative for perioperative pain management in laparoscopic cholecystectomy in a middle-income country.

BACKGROUND: Laparoscopic cholecystectomy is known for its minimally invasive nature, but postoperative pain management remains challenging. Despite the enhanced recovery after surgery (ERAS) protocol, regional analgesic techniques like modified perichondral approach to thoracoabdominal nerve block (M-TAPA) show promise. Our retrospective study evaluates M-TAPA's efficacy in postoperative pain control for laparoscopic cholecystectomy in a middle-income country. METHODS: This was a retrospective case-control study of laparoscopic cholecystectomy patients at Hospital General de Mexico in which patients were allocated to the M-TAPA or control group. The data included demographic information, intraoperative variables, and postoperative pain scores. M-TAPA blocks were administered presurgery. OUTCOMES: opioid consumption, pain intensity, adverse effects, and time to rescue analgesia. Analysis of variance (ANOVA) compared total opioid consumption between groups, while Student's t test compared pain intensity and time until the first request for rescue analgesia. RESULTS: Among the 56 patients, those in the M-TAPA group had longer surgical and anesthetic times (p < 0.001), higher ASA 3 scores (25% vs. 3.12%, p = 0.010), and reduced opioid consumption (p < 0.001). The M-TAPA group exhibited lower postoperative pain scores (p < 0.001), a lower need for rescue analgesia (p = 0.010), and a lower incidence of nausea/vomiting (p = 0.010). CONCLUSION: Bilateral M-TAPA offers effective postoperative pain control after laparoscopic cholecystectomy, especially in middle-income countries, by reducing opioid use and enhancing recovery.

El postacondicionamiento del miocardio con remifentanil en el corazón aislado y perfundido de rata / Myocardial postconditioning with remifentanyl in the isolated perfused rat heart

Resumen: La isquemia miocárdica perioperatoria es un evento observado durante la cirugía en pacientes de alto riesgo y aumenta significativamente la morbimortalidad postoperatoria. El corazón puede tolerar los efectos de la lesión aguda por la isquemia-reperfusión (I/R) si se aplican varios ciclos cortos de I/R previos a la isquemia miocárdica sostenida. Esta estrategia cardioprotectora puede ser usada previamente (preacondicionamiento isquémico) o posteriormente (postacondicionamiento isquémico) al período de isquemia sostenida letal. El condicionamiento farmacológico consiste en el uso de fármacos para obtener efectos cardioprotectores similares al condicionamiento isquémico. Los opioides se han utilizado en el condicionamiento farmacológico, en particular el remifentanil es el más extensamente estudiado en la cardioprotección. Estudios previos demuestran que protege contra el daño por la I/R aplicándolo pre, trans y postreperfusión tanto en estudios experimentales como en la práctica clínica. En este trabajo se estudia el postacondicionamiento inducido con remifentanil en el modelo de Langendorff de corazón aislado y perfundido de rata. Este modelo permite reproducir la isquemia miocárdica en el corazón aislado de un animal anestesiado. Las variables registradas fueron: presión intraventricular izquierda (PVI), frecuencia cardíaca (FC) y actividad contráctil del corazón expresada como el trabajo cardíaco (TC = PVI × FC). La isquemia se produjo al suspender la perfusión de la solución Krebs-Henseleit durante 30 minutos, posteriormente se estableció la reperfusión durante dos horas, observándose la respuesta del corazón aislado en las diferentes condiciones. En los corazones control con I/R, el TC disminuyó un 40%. Por otro lado, el remifentanil recuperó los niveles basales de TC del control sin I/R, demostrando su efecto cardioprotector.

Abstract: Perioperative myocardial ischemia can occur during surgery in high-risk patients, which could increase postoperative morbidity and mortality. The heart can tolerate the effects of acute ischemia-reperfusion (I/R) injury if several short cycles of I/R are applied prior to sustained myocardial ischemia. This strategy is used before (ischemic preconditioning) or after (ischemic postconditioning) sustained lethal ischemia. In pharmacological conditioning, drugs are used to obtain cardioprotective effects like ischemic preconditioning. Opioids have been used in pharmacological conditioning. Remifentanyl is the most extensively studied opioid in cardioprotection. Previous studies show that remifentanyl protects against I/R damage by applying it pre, trans and post-reperfusion in experimental studies and in clinical practice. In this work we studied the postconditioning induced with remifentanyl in the Langendorff model of isolated and perfused rat heart. This model reproduces myocardial ischemia in the heart isolated from an anesthetized animal. The variables recorded were left intraventricular pressure (LVP), heart rate (HR), and heart contractile activity expressed as cardiac work (TC = LVP × HR). Ischemia occurred when the perfusion was stopped for 30 minutes. Later, reperfusion was restored for two hours, observing the response of the isolated heart under the different conditions. In control hearts with I/R, the TC decreased by 40%. On the other hand, remifentanyl recovered the basal levels of TC control without I/R. Further studies are needed to evaluate the effectiveness of remifentanyl postconditioning in daily clinical practice.

Influence of intravenous fentanyl or dexmedetomidine infusions, combined with lidocaine and ketamine, on cardiovascular response, sevoflurane requirement and postoperative pain in dogs anesthetized for unilateral mastectomy.

OBJECTIVE: To compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical trial. ANIMALS: A total of 29 female dogs with mammary tumors. METHODS: Premedication consisted of intramuscular acepromazine and morphine. General anesthesia was induced with intravenous propofol and maintained with sevoflurane. Dogs were randomized to be administered intravenous DLK [dexmedetomidine 1 µg kg-1 loading dose (LD) and 1 µg kg-1 hour-1; lidocaine 2 mg kg-1 LD and 3 mg kg-1 hour-1; ketamine 1 mg kg-1 LD and 0.6 mg kg-1 hour-1; n = 14] or FLK (fentanyl 5 µg kg-1 LD and 9 µg kg-1 hour-1; same doses of lidocaine and ketamine; n = 15) during anesthesia. Cardiorespiratory variables and end-tidal sevoflurane (Fe'Sevo) were recorded during surgery. The number of dogs administered ephedrine to treat arterial hypotension [mean arterial pressure (MAP) < 60 mmHg] was recorded. Meloxicam was administered to both groups. Postoperative pain and rescue analgesia requirement were assessed for 24 hours using the short form of the Glasgow Composite Measure Pain Scale. Data were compared using a mixed effects model or a Mann-Whitney test. RESULTS: More dogs required ephedrine in FLK than in DLK (67% versus 7%). Heart rate was not significantly different between groups, whereas lower values of MAP (p ≤ 0.01) and Fe'Sevo (p = 0.018) were observed in FLK than in DLK. Rescue analgesia was administered to 2/15 dogs in FLK and 0/14 dogs in DLK. CONCLUSIONS AND CLINICAL RELEVANCE: Based on the cardiovascular response during surgery, intraoperative infusions of FLK and DLK provided adequate antinociception. Infusion of DLK provided greater stability of blood pressure. Both protocols resulted in minimal need for additional analgesia within 24 hours postoperatively.

Control of motivation for sucrose in the paraventricular hypothalamic nucleus by dynorphin peptides and the kappa opioid receptor.

The dynorphin peptides are the endogenous ligands for the kappa opioid receptor (KOR) and regulate food intake. Administration of dynorphin-A1-13 (DYN) in the paraventricular hypothalamic nucleus (PVN) increases palatable food intake, and this effect is blocked by co-administration of the orexin-A neuropeptide, which is co-released with DYN in PVN from neurons located in the lateral hypothalamus. While PVN administration of DYN increases palatable food intake, whether it increases food-seeking behaviors has yet to be examined. We tested the effects of DYN and norBNI (a KOR antagonist) on the seeking and consumption of sucrose using a progressive ratio (PR) and demand curve (DC) tasks. In PVN, DYN did not alter the sucrose breaking point (BP) in the PR task nor the elasticity or intensity of demand for sucrose in the DC task. Still, DYN reduced the delay in obtaining sucrose and increased licks during sucrose intake in the PR task, irrespective of the co-administration of orexin-A. In PVN, norBNI increased the delay in obtaining sucrose and reduced licks during sucrose intake in the PR task while increasing elasticity without altering intensity of demand in the DC task. However, subcutaneous norBNI reduced the BP for sucrose and increased the delay in obtaining sucrose in the PR task while reducing the elasticity of demand. Together, these data show different effects of systemic and PVN blockade of KOR on food-seeking, consummatory behaviors, and incentive motivation for sucrose and suggest that KOR activity in PVN is necessary but not sufficient to drive seeking behaviors for palatable food.

Comparison of opioid use disorder patients with and without problematic internet use in terms of impulsivity and attention deficit hyperactivity disorder.

OBJECTIVE: To investigate attention deficit and hyperactivity disorder (ADHD) symptoms and impulsivity among individuals diagnosed with opioid use disorder (OUD) who also exhibit symptoms of problematic internet use (PIU). METHODS: The study involved the participation of 360 patients with OUD enrolled at an alcohol and drug addiction treatment center (ADATC) from October to December 2022. Various assessment tools were administered, including Young's Internet Addiction Scale (YIAS), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Barratt Impulsiveness Scale (BIS), and Adult ADHD Self-Report Scale (ASRS). PIU was identified by YIAS scores equal to or exceeding 50. RESULTS: Most participants diagnosed with OUD had comorbid PIU, with high levels of depression, anxiety, and ADHD symptoms. Both BDI and BAI scores were significantly increased in the PIU group compared to the non-PIU group (p < 0.001). Significant differences were observed in BIS Motor Impulsivity, Attentional Impulsivity, and total scores, indicating higher impulsivity in the PIU group (all p < 0.001). Additionally, higher ASRS scores were found in the PIU group (p < 0.001). CONCLUSION: These findings highlight the importance of addressing PIU and comorbidities in OUD treatment. Interventions targeting ADHD symptoms and emotional well-being may benefit PIU management.

Transdermal Opioids and the Quality of Life of the Cancer Patient: A Systematic Literature Review.

OBJECTIVE: This systematic literature review aims to evaluate the effectiveness of transdermal opioids in managing cancer pain and their impact on the quality of life (QoL) of patients. DATA SOURCES: A systematic literature review conducted following the PRISMA protocol, focusing on randomized clinical trials found in the Lilacs, Embase, PubMed, and SciELO databases over the last 20 years. STUDY SELECTION AND DATA EXTRACTION: We included randomized clinical trials, published in English, Portuguese, or Spanish, which assessed the impact of transdermal opioids on the QoL. Data extraction was facilitated using the Rayyan app. DATA SYNTHESIS: Six articles meeting the inclusion and exclusion criteria were analyzed. These studies covered a population ranging from 24 to 422 cancer patients experiencing moderate to severe pain. The risk of bias was assessed in each study, generally being categorized as uncertain or high. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The findings indicate that the analgesic effectiveness and side effects of transdermal formulations (specifically buprenorphine and fentanyl) for managing moderate to severe cancer pain are comparable to, or in some cases superior to, those of oral opioids traditionally employed. CONCLUSIONS: Transdermal therapy was suggested to have several advantages over oral opioid therapy in enhancing cancer patients' QoL. These benefits span various dimensions, including pain management, physical functioning, mental health, vitality, overall patient improvement, anger/aversion, strength/activity, general QoL, cognitive and emotional functions, fatigue, and insomnia.

Neonatal Abstinence Syndrome and Corresponding Pharmacotherapy Approaches from 2 University-affiliated Neonatal Intensive Care Units in Puerto Rico (2018-2020).

OBJECTIVE: Neonatal abstinence syndrome (NAS) is a set of drug withdrawal symptoms suffered by neonates exposed to drugs in utero. Several studies have widely described NAS incidence and treatment approach; however, little is known regarding the incidence and manifestations of this disease in Puerto Rico (PR). The principal aim of this study was to describe NAS incidence in the neonatal units of hospitals affiliated with the University of PR in terms of occurrence, clinical manifestations, and treatment approaches. METHODS: Our study evaluated the medical records of NAS babies diagnosed from 2018 through 2020 at 2 hospitals affiliated with the University of PR Medical Sciences Campus. Descriptive and inferential statistics were employed to analyze trends. RESULTS: We identified 12 neonates diagnosed with NAS, 5 with low birthweights (<2500 g); for a NAS incidence of 2 cases per 1000 admitted for the 3 years of recollected data. The urine toxicology results revealed that 9 had experienced intrauterine polydrug exposure. Phenobarbital loading dose were determined on the day of diagnosis (indicated by Finnegan score). The first manifestation of NAS symptoms varied: 8 neonates showed symptoms within 48 hours after birth, whereas 4 had withdrawal symptoms within 72-120 hours of their births. Differences between dosing practices and guidelines were observed, ranging from a 0.69% to a 25% difference during treatment initiation. CONCLUSION: Further research on the incidence of NAS in PR (national level) is needed for a deeper understanding that we hope will lead to the development of enhanced treatment protocols in PR.

Analgesic and Anti-inflammatory Potential of the New Tetrahydropyran Derivative (2s,6s)-6-ethyl-tetrahydro-2h-pyran-2-yl) Methanol.

BACKGROUND: The development of analgesic and anti-inflammatory drugs plays a crucial role in modern medicine, aiming to alleviate pain and reduce inflammation in patients. Opioids and nonsteroidal anti-inflammatory drugs are groups of drugs conventionally used to treat pain and inflammation, but a wide range of adverse effects and ineffectiveness in some pathological conditions leads us to search for new drugs with analgesic and anti-inflammatory properties. OBJECTIVES: In this regard, the authors intend to investigate the ((2s,6s)-6-ethyl-tetrahydro-2h-pyran- 2-yl) methanol compound (LS20) on pain and acute inflammation. METHODS: Male Swiss mice were evaluated using acetic acid-induced abdominal writhing, formalin, and tail-flick as models of nociceptive evaluation and edema paw, air pouch and cell culture as models of inflammatory evaluation besides the rotarod test for assessment of motor impairment. RESULTS: The compound showed an effect on the acetic acid-induced abdominal writhing, formalin and tail-flick tests. Studying the mechanism of action, reversion of the antinociceptive effect of the compound was observed from previous intraperitoneal administration of selective and non-selective opioid antagonists on the tail flick test. In addition, the compound induced an antiedematogenic effect and reduced leukocyte migration and the production of pro-inflammatory cytokines in the air pouch model. LS20 was able to maintain cell viability, in addition to reducing cell production of TNF-α and IL-6. CONCLUSION: In summary, the LS20 compound presented an antinociceptive effect, demonstrating the participation of the opioid system and an anti-inflammatory effect related to the inhibition of pro-inflammatory cytokine production. The compound also demonstrated safety at the cellular level.

Severe cerebral edema related to oral methadone: A case report and literature review.

Introduction: Opioids are widely used for pain management, and increased intracranial pressure (ICP) has been evidenced in some cases. We reported a patient with severe cerebral edema after initiating methadone and its complete resolution upon discontinuing the medication. Additionally, a review of the literature is made. Case report: A 53-year-old woman patient with a history of systemic lupus erythematosus developed mechanic chronic lower back pain, refractory to conventional treatments. She presented improvement with oxycodone. She withdrew this medication due to a lack of supplies in her country (Colombia) and showed withdrawal symptoms. She consulted the emergency department, where oral methadone was started and symptom control was achieved. Three days after admission, she presented intense headaches and emesis. A brain CT scan was performed in which severe cerebral edema was appreciated. Methadone was discontinued, and neurological symptoms quickly disappeared. A follow-up brain CT scan was performed later, finding full resolution of the edema. Conclusion: A case of severe cerebral edema associated with the initiation of oral methadone and its rapid resolution without neurological sequelae after its withdrawal is presented, clinicians must be attentive to this adverse event.

Methadone Requires the Co-Activation of µ-Opioid and Toll-Like-4 Receptors to Produce Extracellular DNA Traps in Bone-Marrow-Derived Mast Cells.

Methadone is an effective and long-lasting analgesic drug that is also used in medication-assisted treatment for people with opioid use disorders. Although there is evidence that methadone activates µ-opioid and Toll-like-4 receptors (TLR-4s), its effects on distinct immune cells, including mast cells (MCs), are not well characterized. MCs express µ-opioid and Toll-like receptors (TLRs) and constitute an important cell lineage involved in allergy and effective innate immunity responses. In the present study, murine bone-marrow-derived mast cells (BMMCs) were treated with methadone to evaluate cell viability by flow cytometry, cell morphology with immunofluorescence and scanning electron microscopy, reactive oxygen species (ROS) production, and intracellular calcium concentration ([Ca2+]i) increase. We found that exposure of BMMCs to 0.5 mM or 1 mM methadone rapidly induced cell death by forming extracellular DNA traps (ETosis). Methadone-induced cell death depended on ROS formation and [Ca2+]i. Using pharmacological approaches and TLR4-defective BMMC cultures, we found that µ-opioid receptors were necessary for both methadone-induced ROS production and intracellular calcium increase. Remarkably, TLR4 receptors were also involved in methadone-induced ROS production as it did not occur in BMMCs obtained from TLR4-deficient mice. Finally, confocal microscopy images showed a significant co-localization of µ-opioid and TLR4 receptors that increased after methadone treatment. Our results suggest that methadone produces MCETosis by a mechanism requiring a novel crosstalk pathway between µ-opioid and TLR4 receptors.

Quadratus lumborum block versus transversus abdominis plane block for inguinal hernia repair: A systematic review and meta-analysis with trial sequential analysis.

INTRODUCTION: Postoperative pain management is crucial for patient recovery with Quadratus Lumborum Block (QLB) and Transversus Abdominis Plane Block (TAPB) emerging as potential techniques. We aimed to compare the analgesic efficacy of QLB and TAPB in patients undergoing inguinal hernia repair. METHODS: We performed a systematic review of Cochrane, EMBASE, and MEDLINE databases to identify randomized controlled trials comparing QLB and TAPB in patients undergoing inguinal hernia repair. Outcomes included postoperative pain and opioid consumption. Statistical analysis was performed using RevMan 5.4. The review protocol was registered at PROSPERO (CRD42023445513). RESULTS: We included five RCTs encompassing 255 patients. QLB was associated with a significant decrease in postoperative pain (MD -0.45; 95% CI -0.75 to -0.14; and p = 0.004; I2  = 94%). However, we found no difference in 24-h opioid consumption between QLB and TAPB groups. CONCLUSION: QLB may offer superior pain reduction. However, its effect on opioid consumption remains unclear.

The impact of cannabis on non-medical opioid use among individuals receiving pharmacotherapies for opioid use disorder: a systematic review and meta-analysis of longitudinal studies.

Background: The relationship between cannabis use and the risk of returning to using opioids non-medically during treatment for opioid use disorder (OUD) remains unclear.Objective: We sought to quantify the impact of cannabis use on the risk of non-medical opioid use among people receiving pharmacotherapies for OUD.Methods: A comprehensive search was performed using multiple databases from March 1 to April 5 of 2023. Eligible studies longitudinally assessed the association between cannabis use and non-medical opioid use among people with OUD receiving treatment with buprenorphine, methadone, or naltrexone. We utilized a random-effects model employing the restricted maximum likelihood method. A sensitivity analysis was conducted to understand potential differences between each OUD treatment modality.Results: A total of 10 studies were included in the final meta-analysis. There were 8,367 participants (38% female). The average follow-up time across these studies was 9.7 months (SD = 3.77), ranging from 4 to 15 months. The pharmacotherapies involved were methadone (76.3%) buprenorphine (21.3%), and naltrexone (2.4%). The pooled odds ratio did not indicate that cannabis use significantly influenced non-medical opioid use (OR: 1.00, 95% CI: 0.97-1.04, p = .98). There is evidence of moderate heterogeneity and publication bias.Conclusion: There was no significant association between cannabis use and non-medical opioid use among patients receiving pharmacotherapies for OUD. These findings neither confirm concerns about cannabis increasing non-medical opioid use during MOUD, nor do they endorse its efficacy in decreasing non-medical opioid use with MOUD. This indicates a need for individualized approaches for cannabis use and challenges the requirement of cannabis abstinence to maintain OUD pharmacotherapies.